TY - JOUR T1 - Quantitative Analysis of Methylation Status of the <em>PAX1</em> Gene for Detection of Cervical Cancer JF - International Journal of Gynecologic Cancer JO - Int J Gynecol Cancer SP - 513-519 LP - 513-519 DO - 10.1111/IGC.0b013e3181c7fe6e VL - 20 IS - 4 AU - Tien-Hung Huang AU - Hung-Chen Lai AU - Hwan-Wun Liu AU - Cuei Jyuan Lin AU - Kai-Hung Wang AU - Dah-Ching Ding AU - Tang-Yuan Chu Y1 - 2010/05/01 UR - http://ijgc.bmj.com/content/20/4/513-519.abstract N2 - Objective: Although aided by high-risk human papillomavirus (HPV) DNA test, early detection of cervical cancer is still a challenge. Hypermethylation of the paired boxed gene 1 (PAX1) was recently reported as a characteristic of cervical cancer. This study designed a quantitative measure of PAX1 methylation and compared its efficacy to the currently available Hybrid Capture 2 (HC2) HPV test in detection of cervical cancer.Methods: Using real-time quantitative methylation-specific polymerase chain reaction, we measured the percentage of PAX1 methylation in cervical scrapings obtained from a hospital-based cohort of women with cervical neoplasia of different severities and compared the efficacy of diagnosis of cervical cancer to that of the HC2 HPV test.Results: From 73 cervical scrapings, with diagnoses of normal (n = 17), cervical intraepithelial neoplasm 1 (CIN1; n = 10), CIN2 (n = 18), CIN3 (n = 14), and invasive cancer (n = 14), the percentage of PAX1 methylation was determined. The percent of methylated reference of invasive cancer (mean [SE], 56.7 [7.1]) was significantly higher than CIN3 (6.5 [2.3]) and the other milder lesions (1.0 [0.3]; P &lt; 0.0001). At a cutoff percent of methylated reference value of 4.5, PAX1 methylation was found in 100% of invasive cancer tissue as compared with 0% of normal tissue, 10% of CIN1, 11% of CIN2, and 43% of CIN3 (P &lt; 0.0001). As a comparison, the HC2 HPV test result was positive in 5.9% of normal tissue, 70% of CIN1, 55.6% of CIN2, 71.4% of CIN3, and 100% of invasive cancer. In addition to cancer tissue, methylation of PAX1 was also found in normal tissue adjacent to the cancer lesion (9/11, 82%) but much less in the remote normal tissues (2/5, 40%), indicating a field methylation.Conclusions: In this hospital-based study, quantitative measurement of PAX1 hypermethylation in cervical scrapings is highly sensitive and is more specific than HC2 in detection of cervical cancer. ER -